Mammals are colonized by microbes in the gastrointestinal (GI) tract, on the skin, and in other epithelial and tissue niches such as the oral cavity, eye surface and vagina. The gastrointestinal tract harbors an abundant and diverse microbial community. It is a complex system, providing an environment or niche for a community of many different species or organisms, including diverse strains of bacteria. Hundreds of different species may form a commensal community in the GI tract in a healthy person, and this complement of organisms evolves from the time of birth and is believed to form a functionally mature microbial population by about 3 years of age. Interactions between microbial strains in these populations and between microbes and the subject, e.g., the subject's immune system, shape the community structure, with availability of and competition for resources affecting the distribution of microbes. Such resources may be food, location and the availability of space to grow or a physical structure to which the microbe may attach. For example, a subject's diet is involved in shaping the GI tract flora.
A healthy microbiota provides the subject with multiple benefits, including colonization resistance to a broad spectrum of pathogens, essential nutrient biosynthesis and absorption, and immune stimulation that plays a role in maintaining a healthy gut epithelium and appropriately controlled systemic immunity. In settings of ‘dysbiosis’ or disrupted symbiosis, microbiota functions can be lost or deranged, resulting in increased susceptibility to pathogens, altered metabolic profiles, or induction of pro-inflammatory signals that can result in local or systemic inflammation or autoimmunity.
The intestinal microbiota reportedly play a significant role in educating the immune system by inducing mechanisms for immune control and regulation. Dysbiotic states of the microbiome may underlie the development of inflammatory states, autoimmunity and hyper-reactive immune states, characterized by disregulation of immune function. Allergies are among the most common health problems affecting the life of patients of all ages. Allergic diseases are recognized as an epidemic by the World Health Organization (WHO). The prevalence of allergies has been reported to be increasing over the past decades. Allergic sensitization in childhood, especially in early childhood and especially to food allergens, is believed to be critical as development of an “allergic phenotype” or “atopy” has been shown to facilitate subsequent sensitization to other allergens. Hence, allergies in childhood can be the first step of an allergic cascade leading to multiple allergies later in life, a process commonly referred to as “atopic march.” For example, children with persistent food hypersensitivity early in life were reported to have a dramatically increased risk to develop allergic rhinitis (hay fever) or asthma later in childhood (Ostblom et al., 2008). Children with milder forms of food hypersensitivity also have been reported to be at increased risk for development of respiratory allergies but to a lesser degree than children with persistent food hypersensitivity. Preventing, avoiding, managing, reducing and modulating the allergic reactions in young patients can acutely influence their allergic profile and alter their allergy profile later in life.
There is a need for a method of preventing or inhibiting immune disorders that are associated with a subject's microbiota. One solution to the problem of treating such disorders, as provided herein, is to provide compositions and methods of their use that can facilitate populating a subject's gastrointestinal tract and/or other bacterial niches with a diverse and useful selection of microbiota, to, e.g., improve or maintain general health, to alter a dysbiosis and/or to treat immune disorders such as allergies and asthma. Shortcomings of the prior art are addressed by providing compositions, formulations and methods for consumption by and administration to mammalian subjects including human subjects.
Commensal bacterial and food allergen sensitization are described by Stefka et al. (Stefka et al (2014) PNAS 111:13145-13150).
Compositions comprising isolated bacterial populations and use thereof are described in international application number PCT/US2013/071758, filed on Nov. 25, 2013, published as WO 2014/082050; and in international application number PCT/US2014/014745, filed on Feb. 4, 2014, published as WO 2014/121302, the entire disclosures of which are hereby incorporated by reference in their entirety for all purposes.